IMAGING in AMD From Fluorescein Angiography To the Spectral Domain OCT G. Soubrane, MD,PhD, FEBO, FARVO Department of Ophthalmology University Paris 12-Creteil, FRANCE

FLUORESCEIN ANGIOGRAPHY  Diagnosis of CNV: Gold standard Leakage through abnormal endothelium and CNV Staining of additional tissue or of RPE Evaluation of inner (vessels) and outer (RPE) retinal barriers Diffusible molecule through choriocapillaris Basis for staging of the disease Age Related Maculopathy vs Age related Macular Degeneration Geographic Atrophy vs Choroidal New Vessels 2

Hard drusen Soft drusen Soft drusen Geographic Atrophy Choroidal New Vessels

LES 2 TYPES DE C Pre epithelial classic Sub epithelial occult Choroidal New Vessels LES 2 TYPES DE C Pre epithelial classic Sub epithelial occult

FA CLASSIFICATION Atrophy Age Related Maculopathy (ARM) RPE changes : hyper or hypopigmentation Drusen : hard, soft, calcified, reticular pseudo-drusen Age related Macular Degeneration (AMD) Atrophy Choroidal new vessels (CNV) : classic , occult (MPS type II), PED serous, fibrovascular ( MPS type I)

INDOCYANIN GREEN ANGIOGRAPHY Normal choroidal circulation ARM : Distinction of various material AMD : Dynamic visualisation of Abnormal network and new-vessels Conversion of occult CNV into sub-epithelial CNV Visualization of CNV inside a PED Diagnosis of polypoidal vasculopathy and chorioretinal anastomosis 6

ARM 7

Hard drusen Soft drusen

AMD Exudative maculopathy Sub-epithelial occult CNV 9

Sub-epithelial occult CNV Progressing sub-epithelial occult CNV: AF : discrete abnormalities without diffusion ICG : early filling of the central feeder vessel perfusing a neovascular network within a dark area late staining of a persistent central plaque 10

Sub- epithelial occult CNV

Natural history:Clinical development of PED Sub-epithelial occultCNV Natural history:Clinical development of PED 12

Fibro vascular PED PED Occult DEP très sombre, visible très tôt, à fort contraste, partiellement envahi par une nappe de néovaisseaux sous épithéliaux – à la phase tardive : hyperfluorescence irrégulière, en inféro temporo-maculaire PED Occult

Natural history Sub-epithelial CNV Proliferation of pre-epithelial classic new vessels In 42%, in 2 to 3 years Angiographies : irreplaceable tools AF : visualization of pre-epithelial classic new vessels ICG : identification of sub-epithelial occult new vessels 14

AMD Exudative maculopathy Chorioretinal anastomosis or Type III 15

Chorioretinal anastomosis • Severe form of neovascularization • Frequency 15% of AMD (4.5% for Japanese*) 30% of vascularized PED  Prognosis for second eye * Am J Ophthalmol. 2007

ICG

AMD Exudative maculopathy Idiopathic polypoidal vasculopathy 18

Idiopathic polypoidal vasculopathy Biomicroscopy 19 19

Idiopathic polypoidal vasculopathy FA ICG

Idiopathic polypoidal vasculopathy 21 21

ICG CLASSIFICATION Atrophy Age Related Maculopathy (ARM) RPE changes : hyper or hypopigmentation Drusen : hard, soft, (reticular pseudo drusen) Age related Macular Degeneration (AMD) Atrophy Choroidal new vessels (CNV) : Sub epithelial occult with RPE elevation Vascularized PED Ingrowth of classic pre epithelial Fibrovascular PED CRA, Polyps

OPTICAL COHERENCE TOMOGRAPHY Direct and indirect symptoms Accumulation of fluid in all retinal layers Changes in the neurosensory retina especially of the photoreceptors Irregularity or elevation of the RPE Quantification of the abnormalities : retinal thickening or thinning 23

CIRRUS SD-OCT SPECTRALIS SD-OCT TOPCON SD-OCT OCT 1 OCT 3 HR-OCT

Spectral OCT Analysis of the outer hyper-reflective layers - external limiting membrane - interface OS/IS - RPE - Bruch membrane Interface Bruch’s membrane RPE External limiting membrane Outer nuclear layer Outer segment Inner segment Spectral OCT

Eye tracking on graph

Sub- epithelial occult CNV Network

Sub- epithelial occult CNV Fovea Junction OS/IS Irregular, fragmented RPE

Sub- epithelial occult CNV VA 20/50 P3

RPE detachment organized with discrete shadowing Sub- epithelial occult CNV Fovea SRF RPE RPE detachment organized with discrete shadowing SRF extensive RPE thinned and irregular

Sub- epithelial occult CNV

Sub- epithelial occult CNV Fovea 6 mm RPE detachment - Elevated RPE with moderate reflectivity no marked shadowing Limited subfoveal SRF small increase in retinal thickness foveal flattening

PED with Spectral Domain OCT b Serous PED dépression fovéale Fovea RD DSR DEP PED Occult Fibro vascular PED

CRA with Spectral OCT FA Late ICG VA: 20/50 CRA Large Cysts FA / OCT: Same aspect of Inner layer Intra-retinaIhemmoCG/ OCT:( More peripheral section) CRA with small PED VA: 20/50 35

PCV with Spectral OCT With SD-OCT, the RPE elevation due to the polyp becomes clearly distinguishable The calipers help to localize the SRF, the PED and the polyp. 37

Visibility of Bruch’s membrane OCT CLASSIFICATION Fluid or not fluid Early detection of fluid Quantification of retinal thickness Response to treatment Outer retinal layers Visibility of Bruch’s membrane IS-OS changes Retinal atrophy Beginning of choroidal analysis In the future Adaptive Optics PED OCT CLASSIFICATION

Evolution of imaging for neovascular AMD Huang OCT Fluorescein Angiography Flower Yannuzzi ICG Angiography Drexler Puliafito SD-OCT Coscas Gass 1967 2000 2006 - 2009 Evolution of Therapy for Neovascular AMD Over the years, treatment for neovascular AMD has evolved from approaches aimed at stabilizing vision to improving visual acuity. Conventional therapies have important limitations, such as lack of specificity, associated retinal destruction, and failure to prevent new vessel formation. Newer treatment options address these limitations. Results of VISION, MARINA, ANCHOR, and PIER have demonstrated that VEGF is a bona fide target of therapy, with activity across subtypes of subfoveal lesions. The introduction of anti-VEGF therapy has raised treatment goals and expectations. Classic, Occult CNV, FV PED Subepithelial CNV 39

Evolution of therapy for neovascular AMD SST Submacular surgery Creteil MPS reports Laser photocoagulation TAP report VIP reports VIM PDT with verteporfin VISION MARINA ANCHOR Anti-VEGF therapy PIER 1980 2000 2006 - 2009 Evolution of Therapy for Neovascular AMD Over the years, treatment for neovascular AMD has evolved from approaches aimed at stabilizing vision to improving visual acuity. Conventional therapies have important limitations, such as lack of specificity, associated retinal destruction, and failure to prevent new vessel formation. Newer treatment options address these limitations. Results of VISION, MARINA, ANCHOR, and PIER have demonstrated that VEGF is a bona fide target of therapy, with activity across subtypes of subfoveal lesions. The introduction of anti-VEGF therapy has raised treatment goals and expectations. Halt progression Improve vision PDT = photodynamic therapy